Bacterial Pathogenesis

Pathogenicity

the ability of a microbe to cause disease by overcoming host defenses

Virulence

is the degree to which a microbe is pathogenic

Normal flora

commensal relationship with the host

Opportunistic infections

take advantage of special situations to grow

Nosocomial infections

acquired in hospitals (aka HAI)

Pathogenic infections

interaction between a specific pathogen and the host leads to disease

Pathogenic infections: bacteria damage host tissues

Toxins produced by bacteria. Damage to host cells as bacteria replicate.

Immunopathology

Immune system damages the host while trying to attack the bacteria.

Outbreak

local

Epidemic

regional/national

Pandemic

international

stages of pathogenesis

exposure, adhesion, invasion/infection

Pathogenesis: Exposure and Adhesion

-Microbes attach to the host at a portal of entry using special cell surface molecules (often mucosal surface like the GI and respiratory tract).

-Adhesion is a specific process. Pili allow for initial contact with a host cell. Other surface proteins (adhesins) allow for attachment to the host.

Adhesion and Common E. coli

have pili that only bind to cells in the large intestine and are typically just part of the normal flora

Adhesion and Pathogenic E. coli

Over 20 different kinds of pili have been identified. Some pili can bind to small intestine, causing diarrhea and food posioning, or to the urinary tract, causing UTIs. Genes for different pili are passed on plasmids.

Invasion

Once the bacteria have attached to cell, they might: colonize the area only, spread to a different area of the body, invade (or enter) the host cell to which it is attached (for intracellular bacteria specifically)

Biofilm

groups of bacteria build a slime layer around themselves. Macrophages cannot get through the biofilm. Difficult to penetrate with antibiotics.

Phagocytosis

process by which our immune cells (macrophages, neutrophils) engulf and digest bacteria

How do immune cells know what to phagocytose?

Bacteria have to be tagged by immune proteins

2 ways to tag the bacteria for phagocytosis

1. Complement proteins- a non-specific tag

   1. C3 is always present in your serum

   2. can attach other many different microbes and foreign proteins

2. Antibodies or immunoglobulins- a specific tag

   1. made by cells B-cells

   2. Can be made as different types (IgG, IgA, etc.)

Capsules

capsule formation is common for bacteria that cause pneumonia and meningitis. Capsules= more invasive

How do capsules and biofilms protect the bacteria

Capsules bind to Factor H in our serum. Factor H degrades complement proteins in the area. When the bacteria gather Factor H from our serum, it protects the bacteria from complement binding.

IgG proteases

cleave the hinge region. separates the variable region and the Fc region.

IgG binding proteins

Bind to the Fc region of the antibody. Prevent binding to the Fc receptor on the phagocytes, so the immune cells cannot grab the bacteria.

Antigenic variation

Process by which pathogens display new surface antigens that are not recognized by antibodies elicited in earlier infection.

Once an infection is established, how is the host damaged?

endotoxins and exotoxins

Toxins

biological potions that improve pathogens ability to invade their host and cause disease

Endotoxins

LPS found the outer membrane of Gm- bacteria. Released when cells divide or die. Produces general inflammation.

Exotoxin

Proteins produced by Gm+ and Gm- bacteria. Produced and released as part of metabolism. Produce specific damage to host cells.

genes for exotoxins are usually found on

plasmids

Four main types of Exotoxins

A-B exotoxins, Membrane-Active exotoxins, superantigens,exoenzymes

A-B exotoxins

Enzymes that inhibit cell functions. Ex: neurotoxins, entertoxins, cytotoxins

Membrane-active exotoxins

cause cell lysis

Superantigens

overstimulate the immune system

Exoenzymes

Breakdown collagen and connective tissue. Allow for spread of the bacteria from the original site of infection.

Enterotoxins

Cause diarrhea and dehydration. Can either prevent the uptake of water from the digestive tract or cause cells to release iron and water

Cholera toxin

induces severe dehydration and cell death by forcing cells in the intestine to secrete water.

Membrane-active exotoxins

Lead to disruption of the plasma membrane and cell death (ie pore forming exotoxins and phospholipases)

Pore-forming exotoxins

Allow influx of water into the cell. cause the cell to lyse. Associated with severe food poisoning.

Phospholipase

Cleave the lipids in the membrane. Cause destabilization of the host membrane and cell death.

Clostridium perfringens

-Causes gas gangrene

-Usually results from a deep wound or injury that breaks the skin.

-Releases a phospholipase that destroys the blood vessels.

1. Prevents immune cells from reaching the bacteria

2. Disrupts the delivery of oxygen to site of infection.

3. The exotoxin (And bacteria) spread from that point and destroy the limb.